The New York City-based HIV Center for Clinical and Behavioral Studies is dedicated to multidisciplinary research that will advance the implementation of the US National HIV/AIDS Strategy - to prevent new infections, improve health outcomes for people living with HIV, and reduce health disparities. In 2011, we are at a defining moment in the HIV epidemic with the emergence of effective biomedical approaches to HIV prevention. Yet, without rigorous behavioral and social science research to ensure uptake and adherence, these approaches will not realize their potential. In this renewal application, we propose important reconceptualizations and reconfigurations mobilizing a diverse and multidisciplinary cadre of senior scientists, early stage investigators, practitioners, and policy-makers from multiple academic, community and public health venues to (1) advance the science of HIV prevention, treatment, and care, providing the building blocks for combination prevention, (2) realize the full potential of biomedical HIV prevention and treatment strategies through the application of behavioral and social science theory and research, and (3) apply principles of implementation science to maximize our public health impact. We propose the following six Cores, reflecting our commitment to breaking new ground while building on documented strengths and accomplishments: (1) the Administrative Core to provide leadership that stimulates and manages innovative research through strategic planning, ensuring the highest scientific standards and ethical integrity, and efficient fiscal operations; (2) the Development Core to promote science innovation, provide internal peer review, and nurture early stage investigators; (3) the Intervention Science Core to provide expertise on intervention development and assessment, stimulate the integration of biomedical and behavioral approaches, and advise on the use of community-based participatory research methodologies; (4) the Statistics, Epidemiology and Data Management Core to provide a centralized resource for innovative research designs, statistical analysis, and data management; (5) the Public Health Practice and Policy Core to apply implementation science and ethical and policy analysis to close the gaps among science, public health practice, and policy; and (6) the New Media Core, to integrate new media and information technologies into HIV research and focus on these environments as areas in need of study. The HIV Center provides a rich, value-added resource to a large number of investigators, practitioners, and policy-makers, while attracting and training new investigators and making innovative, scientific, programmatic, and policy contributions that respond to the evolving HIV/AIDS epidemic on a national and international level.